A Randomized Placebo-Controlled Phase III Study of Duloxetine for Treatment of Aromatase Inhibitor (AI)-Associated Musculoskeletal Symptoms in Women with Early Stage Breast Cancer

Women with histologically confirmed estrogen receptor (ER) and/or progresterone receptor (PgR) positive invasive carcinoma of the breast with no evidence of metastatic disease (Stage I-III); must have completed mastectomy or breast sparing surgery and must have recovered from all side effects of surgery. If treated with chemo or radiation therapy, treatments must be completed > 28 days prior to registration and recovered from all Grade 2 or higher side effects with the exception of alopecia and peripheral neuropathy. Concurrent bisphosphonate and trastuzumab therapies allowed; must be post-menopausal as defined by one of the following: >/= 12 months since last menstrual period, prior bilateral oophorectomy, or previous hysterectomy with one or both ovaries left in place AND (unless >/= 60 years of age) FSH values consistent with institutional values for post menopausal state; must be taking the following AI and doses for > 21 days, but < 36 months, prior to registration with plans to continue > 180 after registration: anastrozole 1 mg daily, letrozole 2.5 mg daily, or exemestane 25 mg daily; must have AI assosicated musculoskeletal symptoms that began or increased after starting AI therapy. New musculoskeletal pain must not be due specifically to fracture or traumatic injury; must have completed S1202 Brief Pain Inventory-Short Form within 7 days prior to registration and have �average pain� of at least 4 on item #4; Zubrod PS 0-2; no known allergy or hypersensitivity to duloxetine or any inactive ingredients in matching placebo; must not have contraindicated concurrent illnesses listed on duloxetine package insert including: current primary psychiatric diagnosis (schizophrenia, psychosis) or suicidal ideation, history or bipolar disorder, or seizure disorder, history of alcohol or other substance abuse or dependence < 365 prior to registration, chronic liver disease, end stage renal disease, uncontrolled narrow-angle glaucoma, clinically significant coagulation disorder; must not take MAO-Inhibitors for 14 days prior to reg or during study treatment, concomitant therapy with heparin and warfarin is not permitted; calculated creatinine clearance > 30 mL/min within 28 days prior to registration; AST and ALT both within 3 x Upper Limit of Normal; total bilirubin within upper limit of normal; must not require selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants during study participation. Patients must have been able to taper and discontinue treatment with these medications > 7 days prior to registration (28 days for fluoxetine), and must not be experiencing antidepressant withdrawal symptoms. Must not have previously taken the serotonin norepinephrine reuptake inhibitors (SNRI) duloxetine or milnacipran. Prior venlafaxine is allowed as long as it was not taken for treatment of pain. NOTE: Patients requiring antidepressants for management of depression are not appropriate candidates for this placebo-controlled study, but those who are on antidepressants for other indications (such as hot flash management) may be able to tolerate a time off of antidepressant therapy; if receiving treatment with narcotics, tramadol, gabapentin, and/or pregabalin, must be taking a stable dose for at least 30 days prior to registration; must be able to complete study questionnaires in English; must not have concurrent medical/arthritic disease that could confound or interfere with evaluation of pain or efficacy including: inflammatory arthritis and cancer involving the bone. Patients may have osteoarthritis; must be willing to submit blood samples for correlative studies